The purpose of this study is to examine the drug interactions between a protease inhibitor (PI)-based regimen including lopinavir/ritonavir (LPV/r) and two forms of contraceptive medications in HIV infected women.

PK parameters of LPV in Arm A at baseline and on Days 17, 18, 19, and 24

Enrollment:

32

Study Completion Date:

January 2007

Detailed Description:

Both PIs and oral contraceptives are metabolized by the same pathway, which significantly decreases the effectiveness of oral contraceptives and limits the contraceptive choices available to HIV infected women. More effective hormonal contraceptive methods are necessary for preventing unintended pregnancy in women taking highly active antiretroviral therapy (HAART). Ortho Evra is a contraceptive patch that was approved by the FDA in 2001; it uses a transdermal contraceptive system, and higher rates of compliance have been associated with its use, compared to oral contraceptives. Because Ortho Evra is administered as a contraceptive patch worn on the skin, it may bypass the metabolic pathway common to both PIs and oral contraceptives, making it a viable contraceptive option for HIV infected women on PI-based regimens. The purpose of the study is to examine the interaction between a PI-based regimen containing LPV/r and two forms of contraceptive medications, Ortho Evra and an oral contraceptive, Ortho Novum (ON 1/35), in HIV infected women.

Participants will be enrolled in this study for 6 weeks and will be assigned to one of two study arms, depending on their HAART regimen at study entry. Participants in both arms will also be stratified by age. Arm A participants will receive 400 mg/100 mg LPV/r twice daily along with two or more nucleoside reverse transcriptase inhibitors (NRTIs). Arm B participants will receive a regimen containing only NRTIs or no HAART. HAART will not be provided by this study. All patients will receive a single dose of ON 1/35 on Day 1 and will start the Ortho Evra contraceptive patch on Day 3. A physical exam, pap smear, pregnancy test, viral load test, CD4 and CD8 counts, and blood collection will occur at or before study entry and on Day 24. Pharmacokinetic analyses will occur on Days 1 through 3, 17 through 19, and 24.

Eligibility

Ages Eligible for Study:

13 Years and older

Genders Eligible for Study:

Female

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria for All Participants:

HIV infected

CD4 count of 200 cells/mm3 or more within 45 days of study entry

HIV-1 RNA viral load less than 55,000 copies/ml within 45 days of study entry

Parent or guardian willing to provide informed consent

Negative pregnancy test within 45 days of study entry

Willing to use acceptable forms of contraception

Agrees not to change current smoking or non-smoking habits

Agrees not to consume caffeine on Day 1, Days 17 through 19, and Day 24 until after the last blood sample of that day is drawn

Agrees not to consume alcohol within 48 hours of PK sampling periods

Patients on methadone maintenance therapy should be on a stable methadone dose for at least 60 days prior to study entry and continue maintenance therapy throughout the study

Inclusion Criteria for Arm A Participants:

Have taken LPV/r for at least 60 consecutive days prior to study entry and taken the same dose twice daily for at least 14 days prior to study entry. Women switching from capsule formulation LPV/r to new tablet formulation of 200mg/50 mg LPV/r must be taking twice-daily doses of this formulation, for a total daily dose of 800 mg/200 mg LPV/r, for at least 7 days prior to study entry.

Inclusion Criteria for Arm B Participants:

Have not taken or currently not taking a PI- or non-nucleoside reverse transcriptase inhibitors (NNRTI-) based regimen for at least 30 days prior to study entry, and not planning on starting PIs or NNRTIs during the 6-week study period. Women who have not been on HAART for at least 30 days prior to study entry are also eligible.

For patients not receiving HAART, documentation that they have been counseled about the benefits of HIV treatment within 90 days of study entry and have elected not to initiate therapy

Anabolic therapies (nandrolone decanoate or megestrol) within 60 days of study entry

Systemic glucocorticoids within 14 days of study entry

Certain medical conditions. More information on this criterion can be found in the protocol.

Need for prolonged bedrest after major surgery

Smokers of ages 35 or older

NNRTIs within 30 days of study entry

Nausea, vomiting, or abdominal pain of Grade 3 or higher within 30 days of study entry

Known allergy or sensitivity to ethinyl estradiol (EE), norelgestromin (NGMN), or components of the Ortho Evra contraceptive patch

Known allergy or sensitivity to norethindrone or components of the ON 1/35 oral contraceptive pill

Serious illness requiring systemic treatment or hospitalization within 14 days of study entry

Undiagnosed abnormal vaginal bleeding

Depo-Provera (medroxyprogesterone acetate) within 180 days of study entry

Lunelle (estradiol cypionate and medroxyprogesterone acetate) within 90 days of study entry

Use of certain medications within 30 days of study entry

Current drug or alcohol use or dependence that, in the opinion of the investigator, may interfere with the study

Unable to adhere to HAART, the Ortho Evra contraceptive patch, or single dose ON 1/35 regimens

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00125983